The present invention relates to a method for preventing, reducing and treating radiation cystitis caused by external beam radiation therapy, which impinges on the urinary bladder and associated structures, comprising administering into the urinary bladder and associated structures a composition comprising hyaluronic acid (HA) having an average molecular weight of not less than 2xc3x97105 Daltons and a pharmaceutically acceptable carrier.
Carcinoma of the prostate is among the most common forms of cancer and of cancer mortality in males. External beam radiation therapy (hereinafter, radiotherapy) is widely used for patients with clinically localized carcinoma of the prostate and is standard therapy for patients diagnosed with extensive local disease (American Joint Committee on Cancer). Radiotherapy also is used for patients with clinically localized carcinoma of the bladder, rectum, uterus and cervix.
Acute effects of radiotherapy on normal tissue are observed during and immediately following a course of radiotherapy. The major complication of radiotherapy, which impinges on the bladder area, is its effect on urinary bladder function resulting in radiation cystitis. Radiation cystitis is defined in terms of bladder pain, increased urinary urgency, increased voiding frequency and increased nocturia. Its duration is usually 3 to 6 months, but can be 24 months or longer. Moreover, serious delayed urinary complications involving lifestyle altering symptoms or requiring hospitalization are observed in 2-7% of patients undergoing radiotherapy for prostate cancer.
It is hypothesized that radiation of the bladder area induces disruption of the glycosaminoglycan (GAG) layer, which lines the inner surface of the urinary bladder. This GAG layer consists of mucopolysaccharides attached to a core protein that, in turn, is bound to a central hyaluronic acid string. This highly viscous, highly hydrophilic GAG layer protects the bladder epithelium against irritants in the urine including, but not limited to, microorganisms, pathogens, microcrystals, proteins, calcium, urea and carcinogens (Nickel et al. 1993. Journal of Urology, 149:716). When this protective barrier is damaged, the bladder epithelium becomes permeable to urinary irritants, resulting in symptoms of bladder pain, increased urinary urgency, increased voiding frequency and increased nocturia. Other symptoms can include, but are not limited to, dysuria, heamaturia, arthritis, spastic colon, low grade fever and irritability.
Methods for treating existing interstitial cystitis include, but are not limited to, hydraulic distention of the urinary bladder, oral amitriptyline or sodium pentosanpolysulfate, intravesical instillation of dimethyl-sulfoxide, oxychlorosene sodium, silver nitrate, heparin, angiostatic steroids, pentosanpolysulfate and hyaluronic acid.
However, what is needed is a method for protecting the urinary bladder from the effects of the radiotherapy so as to prevent, reduce and treat the radiation cystitis caused by radiotherapy that impinges on the bladder area.
A method is provided for preventing, reducing and treating radiation cystitis caused by radiotherapy that impinges on the urinary bladder of an animal, including a human, comprising administering into the bladder of the animal a composition comprising HA, having an average molecular weight of not less than 2xc3x97105 Daltons, and a pharmaceutically acceptable carrier, wherein the HA is administered in an amount effective to prevent, reduce and treat the radiation cystitis.
It is an object of the present invention to provide a method for preventing radiation cystitis.
It is another object of the present invention to provide a method for preventing radiation cystitis that has minimal side effects.
It is another object of the present invention to provide a method for preventing radiation cystitis that is minimally invasive.
It is another object of the present invention to provide a method for preventing radiation cystitis in an individual undergoing radiotherapy for bladder cancer.
It is another object of the present invention to provide a method for preventing radiation cystitis in an individual undergoing radiotherapy for prostate cancer.
It is another object of the present invention to provide a method for preventing radiation cystitis in an individual undergoing radiotherapy for rectal cancer.
It is another object of the present invention to provide a method for preventing radiation cystitis in an individual undergoing radiotherapy for uterine cancer.
It is another object of the present invention to provide a method for preventing radiation cvstitis in an individual undergoing radiotherapy for cervical cancer.
It is another object of the present invention to provide a method for reducing radiation cystitis
It is another object of the present invention to provide a method for reducing radiation cystitis that has minimal side effects.
It is another object of the present invention to provide a method for reducing radiation cystitis that is minimally invasive.
It is another object of the present invention to provide a method for reducing radiation cystitis in an individual undergoing radiotherapy for bladder cancer.
It is another object of the present invention to provide a method for reducing radiation cystitis in an individual undergoing radiotherapy for prostate cancer.
It is another object of the present invention to provide a method for reducing radiation cystitis in an individual undergoing radiotherapy for rectal cancer.
It is another object of the present invention to provide a method for reducing radiation cystitis in an individual undergoing radiotherapy for uterine cancer.
It is another object of the present invention to provide a method for reducing radiation cystitis in an individual undergoing radiotherapy for cervical cancer.
It is another object of the present invention to provide a method for treating radiation cystitis after completion of a course of radiotherapy.
It is another object of the present invention to provide a method for treating radiation cystitis after completion of a course of radiotherapy that has minimal side effects.
It is another object of the present invention to provide a method for treating radiation cystitis after completion of a course of radiotherapy that is minimally invasive.
It is another object of the present invention to provide a method for treating radiation cystitis in an individual after completion of a course of radiotherapy for bladder cancer.
It is another object of the present invention to provide a method for treating radiation cystitis in an individual after completion of a course of radiotherapy for prostate cancer.
It is another object of the present invention to provide a method for treating radiation cystitis in individuals after completion of a course of radiotherapy for rectal cancer.
It is another object of the present invention to provide a method for treating radiation cystitis in an individual after completion of a course of radiotherapy for uterine cancer.
It is another object of the present invention to provide a method for treating radiation cystitis in an individual after completion of a course of radiotherapy for cervical cancer.